Antibiotics for PPROM

SourceLocation and Type of TrialInterventionMaternal OutcomePerinatal/Neonatal Outcome
Kenyon et al (ORACLE I trial)372Urban hospitals in many countries; RPCT4826 women with PPROM were randomly assigned to receive 250 mg erythromycin (n = 1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid; n = 1212), both (n = 1192), or placebo (n = 1225), 4 times daily for 10 d or until delivery.Significant prolongation of gestation (40.7% females delivered within 48 hours in the placebo group, vs 34.8% in the erythromycin-only group, P = .004)was seen in mothers treated with any erythromycin combination but no differences were seen in rates of maternal infection or the need for additional antibiotics.The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Fewer infants (P = .08) had the primary composite outcome in the erythromycin group (151 of 1190 (12.7%)) than in the placebo group (86 of 1225 (15.2%)). Among the 2260 singletons in this comparison, significantly fewer had the composite primary outcome in the erythromycin group (125 of 1111 (11.2%) vs 166 of 1149 (14.4%), P = .02).
Magwali et al375Zimbabwe; Harare Maternity Hospital; RCT171 women with PPROM between 26 and 36 wk gestation were randomized to a course of prophylactic Augmentin or no prophylactic antibiotic treatment at all. The calculated sample size was 72 women per group.Although there was a trend towards higher maternal febrile morbidity rate in the group that did not receive any treatment, no statistical significance was achieved. The women in the treatment group had a significant prolongation of gestation, with 37.8% of the mothers in the this group delivering within 48 hours of membrane rupture compared to 58.1% in the group that received no treatment (P = .01247). More mothers in the treatment group (43.9%) delivered between 48 hours and 7 d after membrane rupture in comparison to the group that did not receive treatment (34.9%). 18% of the mothers in the treatment group delivered after 7 d, as opposed to only 7% of the mothers in the group that received no treatment. (P = 0.01247).The neonatal outcome measures in the 2 groups (birth weight, Apgar scores, neonatal death due to sepsis, neonatal sepsis) were not significantly different.
Ovalle-Sallas et al374Sites in Chile and USA; urban hospital setting; DBRCT79 women with PPROM were randomized to receive IV clindamycin plus gentamicin for 7 d (n = 39) or to the control group (n = 40).Overall, incidence of premature births (<37 wk and <34 wk gestation) was not reduced. In women with infections who received antibiotics, incidence of premature birth (<34 wk) was significantly lower than those patients who received placebo (44.4% vs 88.9%, respectively, P < .05).Neonatal outcomes were unclear as the trial was stopped after the treatment group showed better maternal outcomes at intermediate analysis.
Almeida et al373Mozambique; urban hospital setting; RCT106 third trimester pregnant women with PPROM were randomized to either oral amoxicillin (0.75 g, 3 times daily) (n = 50) or placebo (n = 56) in a blinded fashion. The patients were hospitalized in bed for 7 d unless contractions started and delivery ensued.The average rupture-to-expulsion interval was 68.4 hours in the placebo group and 91.7 hours in the amoxicillin group (P = .28). Hospital stay (3.0 vs 4.3 d, P = .03) was prolonged by 43% in the amoxicillin group. Rates of hemorrhage and postnatal endometritis-myometritis did not differ significantly in the 2 groups.Birth weight and stillbirth rate did not differ significantly in the 2 groups. There was a trend towards longer duration of hospital stay among newborns in the amoxicillin group suffering neonatal death (1.6 vs 6.5 d, P = .06).